Long-term efficacy of a rural community-based integrated intervention for prevention and management of chronic obstructive pulmonary disease: a cluster randomized controlled trial in China's rural areas

This study aimed to assess the efficacy of a rural community-based integrated intervention for early prevention and management of chronic obstructive pulmonary disease (COPD) in China. This 18-year cluster-randomized controlled trial encompassing 15 villages included 1008 patients (454 men and 40 women in the intervention group [mean age, 54 ± 10 years]; 482 men and 32 women in the control group [mean age, 53 ± 10 years]) with confirmed COPD or at risk for COPD. Villages were randomly assigned to the intervention or the control group, and study participants residing within the villages received treatment accordingly. Intervention group patients took part in a program that included systematic health education, smoking cessation counseling, and education on management of COPD. Control group patients received usual care. The groups were compared after 18 years regarding the incidence of COPD, decline in lung function, and mortality of COPD. COPD incidence was lower in the intervention group than in the control group (10% vs 16%, <0.05). A decline in lung function was also significantly delayed in the intervention group compared to the control group of COPD and high-risk patients. The intervention group showed significant improvement in smoking cessation compared with the control group, and smokers in the intervention group had lower smoking indices than in the control group (350 vs 450, <0.05). The intervention group also had a significantly lower cumulative COPD-related death rate than the control group (37% vs 47%, <0.05). A rural community-based integrated intervention is effective in reducing the incidence of COPD among those at risk, delaying a decline in lung function in COPD patients and those at risk, and reducing mortality of COPD.

Clinical impact of Achromobacter xylosoxidans colonization/infection in patients with cystic fibrosis

The rate of diagnosis of colonization/infection of the airways with Achromobacter xylosoxidans has increased in cystic fibrosis patients, but its clinical significance is still controversial. This retrospective, case-control study aimed to evaluate the clinical impact of A. xylosoxidans colonization/infection in cystic fibrosis patients. Individuals who were chronically colonized/infected (n=10), intermittently colonized/infected (n=15), and never colonized/infected with A. xylosoxidans (n=18) were retrospectively evaluated during two periods that were 2 years apart. Demographic characteristics, clinical data, lung function, and chronic bacterial co-colonization data were evaluated. Of the total study population, 87% were pediatric patients and 65.1% were female. Individuals chronically colonized/infected with A. xylosoxidans had decreased forced expiratory volume in 1 s (51.7% in the chronic colonization/infection group vs 82.7% in the intermittent colonization/infection group vs 76% in the never colonized/infected group). Compared with the other two groups, the rate of co-colonization with methicillin-resistant Staphylococcus aureus was higher in individuals chronically colonized/infected with A. xylosoxidans (P=0.002). Changes in lung function over 2 years in the three groups were not significant, although a trend toward a greater decrease in lung function was observed in the chronically colonized/infected group. Compared with the other two groups, there was a greater number of annual hospitalizations in patients chronically colonized/infected with A. xylosoxidans (P=0.033). In cystic fibrosis patients, there was an increased frequency of A. xylosoxidans colonization/infection in children, and lung function was reduced in patients who were chronically colonized/infected with A. xylosoxidans. Additionally, there were no differences in clinical outcomes during the 2-year period, except for an increased number of hospitalizations in patients with A. xylosoxidans.

Issues in the Transatlantic Trade and Investment Partnership: A critical discourse analysis

Negotiating trade agreements is an important part of government trade policies, economic planning and part of the globally operating trading system of today. European Union and the United States have been active in the formation of trade agreements in global comparison. Now these two economic giants are engaged in negotiations to form their own trade agreement, the so called Transnational Trade and Investment Partnership (TTIP). The purpose of this thesis is to understand the reasons for making a trade agreement between two economic areas and understanding the issues it may include in the case of the TTIP. The TTIP has received a great deal of attention in the media. The opinions towards the partnership have been extreme, and the debate has been heated. The purpose of this study is to introduce the nature of the public discussion regarding the TTIP from Spring 2013 until 2014. The research problem is to find out what are the main issues in the agreement and what are the values influencing them. The study was conducted applying methods of critical discourse analysis to the chosen data. This includes gathering the issues from the data based on the attention each has received in the discussion. The underlying motives for raising different issues were analysed by investigating the authors’ position in the political, economic and social circuits. The perceived economic impacts of the TTIP are also under analysis with the same criteria. Some of the most respected economic newspapers globally were included in the research material as well as papers or reports published by the EU and global organisations. The analysis indicates a clear dichotomy of the attitudes towards the TTIP. Key problems include lack of transparency in the negotiations, the misunderstood investor-state dispute settlement, the constantly expanding regulatory issues and the risk of protectionism. The theory and data does suggest that the removal of tariffs is an effective tool for reaching economic gains in the TTIP and even more effective would be the reducing of non-tariff barriers, such as protectionism. Critics are worried over the rising influence of corporations over governments. The discourse analysis reveals that the supporters of the TTIP have values related to increasing welfare through economic growth. Critics do not deny the economic benefits but raise the question of inequality as a consequence. Overall they represent softer values such as sustainable development and democracy as a counter-attack to the corporate values of efficiency and the maximising of profits.

Model-based testing of software systems : functionality and performance

Software is a key component in many of our devices and products that we use every day. Most customers demand not only that their devices should function as expected but also that the software should be of high quality, reliable, fault tolerant, efficient, etc. In short, it is not enough that a calculator gives the correct result of a calculation, we want the result instantly, in the right form, with minimal use of battery, etc. One of the key aspects for succeeding in today's industry is delivering high quality. In most software development projects, high-quality software is achieved by rigorous testing and good quality assurance practices. However, today, customers are asking for these high quality software products at an ever-increasing pace. This leaves the companies with less time for development. Software testing is an expensive activity, because it requires much manual work. Testing, debugging, and verification are estimated to consume 50 to 75 per cent of the total development cost of complex software projects. Further, the most expensive software defects are those which have to be fixed after the product is released. One of the main challenges in software development is reducing the associated cost and time of software testing without sacrificing the quality of the developed software. It is often not enough to only demonstrate that a piece of software is functioning correctly. Usually, many other aspects of the software, such as performance, security, scalability, usability, etc., need also to be verified. Testing these aspects of the software is traditionally referred to as nonfunctional testing. One of the major challenges with non-functional testing is that it is usually carried out at the end of the software development process when most of the functionality is implemented. This is due to the fact that non-functional aspects, such as performance or security, apply to the software as a whole. In this thesis, we study the use of model-based testing. We present approaches to automatically generate tests from behavioral models for solving some of these challenges. We show that model-based testing is not only applicable to functional testing but also to non-functional testing. In its simplest form, performance testing is performed by executing multiple test sequences at once while observing the software in terms of responsiveness and stability, rather than the output. The main contribution of the thesis is a coherent model-based testing approach for testing functional and performance related issues in software systems. We show how we go from system models, expressed in the Unified Modeling Language, to test cases and back to models again. The system requirements are traced throughout the entire testing process. Requirements traceability facilitates finding faults in the design and implementation of the software. In the research field of model-based testing, many new proposed approaches suffer from poor or the lack of tool support. Therefore, the second contribution of this thesis is proper tool support for the proposed approach that is integrated with leading industry tools. We o er independent tools, tools that are integrated with other industry leading tools, and complete tool-chains when necessary. Many model-based testing approaches proposed by the research community suffer from poor empirical validation in an industrial context. In order to demonstrate the applicability of our proposed approach, we apply our research to several systems, including industrial ones.

Extreme Observables and Optimal Measurements in Quantum Theory

Optimization of quantum measurement processes has a pivotal role in carrying out better, more accurate or less disrupting, measurements and experiments on a quantum system. Especially, convex optimization, i.e., identifying the extreme points of the convex sets and subsets of quantum measuring devices plays an important part in quantum optimization since the typical figures of merit for measuring processes are affine functionals. In this thesis, we discuss results determining the extreme quantum devices and their relevance, e.g., in quantum-compatibility-related questions. Especially, we see that a compatible device pair where one device is extreme can be joined into a single apparatus essentially in a unique way. Moreover, we show that the question whether a pair of quantum observables can be measured jointly can often be formulated in a weaker form when some of the observables involved are extreme. Another major line of research treated in this thesis deals with convex analysis of special restricted quantum device sets, covariance structures or, in particular, generalized imprimitivity systems. Some results on the structure ofcovariant observables and instruments are listed as well as results identifying the extreme points of covariance structures in quantum theory. As a special case study, not published anywhere before, we study the structure of Euclidean-covariant localization observables for spin-0-particles. We also discuss the general form of Weyl-covariant phase-space instruments. Finally, certain optimality measures originating from convex geometry are introduced for quantum devices, namely, boundariness measuring how ‘close’ to the algebraic boundary of the device set a quantum apparatus is and the robustness of incompatibility quantifying the level of incompatibility for a quantum device pair by measuring the highest amount of noise the pair tolerates without becoming compatible. Boundariness is further associated to minimum-error discrimination of quantum devices, and robustness of incompatibility is shown to behave monotonically under certain compatibility-non-decreasing operations. Moreover, the value of robustness of incompatibility is given for a few special device pairs.

Explaining the intention to play and behavior of playing sports betting games of young Finnish adults : an application of the theory of planned behavior

The aim of this Master’s Thesis was to examine the determinants of intention and behavior of playing sports betting games in order to explain the intention to play in a more precise way and to be able to understand the behavior of playing. The theory of planned behavior was applied in explaining the intention of young Finnish adults aged 18 to 34. A quantitative research method was applied and an online survey was sent to the students of Lappeenranta University of Technology and to the subscribers of Urheilulehti in order to reach a sample that present the young population of Finland. The theory of the study focused on the theory of planned behavior and its antecedents, attitude towards behavior, subjective norms, perceived behavioral control as well as motivation. By analyzing the data, causal relationships were found through which the explanation of intention was possible. The results showed that attitude towards playing, subjective norms, perceived behavioral control and motivation impact the formation of intention significantly. The results also indicated that intention impacts significantly to the playing frequency.

Citizen Jane : exploring the relationship between gender and cellular phones in societies of control

In this thesis, I argue that the mutually productive relationship between women (as gendered subjects) and cellular phone technology is one of control. Women use cellular phones to organize, manage and otherwise control the multiplicity of tasks required of them on a daily basis. At the same time, through using cell phones, women participate in regimes of control including surveillance and persistent connection. I explore this relationship at the level of everyday practice, and conclude by speculating about this relationship at a wider level of social control and organization. This argument emerges from the critical approach suggested by Slack and Wise (2005), who argue that technology and culture are inseparable. They provide articulations and assemblages as tools of analysis. I situate this analysis more broadly within Foucault's (1991) work on govemmentality, in its modem form of societies of control (Deleuze, 1995b).

The acute effects of differential dietary fatty acids on PDHa activity in human skeletal muscle at the onset of exercise

Pyruvate dehydrogenase (PDH) is an important regulator of carbohydrate oxidation during exercise and its activity can be down-regulated by an increase in dietary fat. The purpose of this study was to determine the acute metabolic effects of differential dietary fatty acids on the activation of PDH in its active form (PDHa) at rest and at the onset of moderate-intensity exercise. University-aged male subjects (n=7) underwent 2 fat loading trials spaced at least 2 weeks apart. Subjects consumed saturated (SFA) or polyunsaturated (PUFA) fat over the course of 5 hours. Following this, participants cycled at 65% VO2 max for 15 min. Muscle biopsies were taken prior to and following fat loading and at 1 min exercise. Plasma free fatty acids increased from 0.15 ± 0.07 to 0.54 ± 0.19 mM over 5 hours with SFA and from 0.1 1 ± 0.04 to 0.35 ±0.13 mM with PUFA. PDHa activity was unchanged following fat loading, but increased at the onset of exercise in the SFA trial, from 1 .4 ± 0.4 to 2.2 ± 0.4 /xmol/min/kg wet wt. This effect was negated in the PUFA trial (1 .2 ± 0.3 to 1 .3 ± 0.3 pimol/min/kg wet wt.). PDH kinase (PDK) was unchanged in both trials, suggesting that the attenuation of PDHa activity with PUFA was a result of changes in the concentrations of intramitochondrial effectors, more specifically intramitochondrial NADH or Ca^*. Our findings suggest that attenuated PDHa activity participates in the preferential oxidation of PUFA during moderateintensity exercise.

Education, sport and myth in the community of Glengarry, Ontario : the athletic career of Roderick R. McLennan. 260 St. Catharines, Ont. : Faculty of Education, Brock University ;

This study examined how the athletic career of Roderick R. McLennan contributed to the popularization and subsequent development of Caledonian games in Ontario during the latter nineteenth century. Initially, the development of Caledonian games during the 1800s was examined to provide a contextual framework for McLennan's career. This investigation revealed that the games emerged from rural athletic events at pioneer working bees in the first quarter of the nineteenth century to regional sporting events by the mid-1800s, and finally into annual federated Caledonian games in 1870. Noteworthy primary source material for this chapter included the John MacGillivray Papers at the National Archives of Canada, the Scottish American Journal (NY) and the files retained by the Glengarry Sport Hall of Fame in Maxville, Ontario. Following the investigation of Caledonian games, McLennan's early athletic career was studied. Analysis of the Roderick and Farquhar McLennan Papers at the Archives of Ontario and the newspapers from the period revealed that McLennan rose to popularity in 1865 through a "Championship of the World" hammer throwing match in Cornwall and two "Starring Tours". The next chapter examined the height of McLennan's career through an investigation of the Roderick McLennan versus Donald Dinnie rivalry of the early .. n 1870s. It was detennined that the rivalry between McLennan and Dinnie, the champion athlete of Highland games in Scotland, was a popular attraction and had an impact on the Toronto and Montreal games of 1870 and the Toronto games of 1872. Finally, the athletic records established by McLennan during the 1860s and 1870s were investigated. These records were examined through the context of a media controversy over McLennan's feats that developed in the early 1880s between two newspapers. This controversy erupted between the Toronto Mail and the Spirit of the Times. Caledonian games in Canada have only been briefly examined and a thorough examination of prominent Canadian figures in this context has yet to be undertaken. This study unearths a prominent Canadian athlete of Scottish decent and details his involvement in the Caledonian games of nineteenth century Ontario.

Effects of intracerebroventricular bombesin administration on local cerebral glucose utilization in the restrained and unrestrained rat

Intracerebroventricular (ICV) administration of bombesin (BN) induces a syndrome characterized by stereotypic locomotion and grooming, hyperactivity and sleep elimination, hyperglycemia and hypothermia, hyperhemodynamics, feeding inhibition, and gastrointestinal function changes. Mammalian BN-like peptides (MBNs), e.g. gastrin-releasing peptide (GRP), Neuromedin C (NMC), and Neuromedin B (NMB), have been detected in the central nervous system. Radio-labeled BN binds to specific sites in discrete cerebral regions. Two specific BN receptor subtypes (GRP receptor and NMB receptor) have been identified in numerous brain regions. The quantitative 2-[14C]deoxyglucose ([14C]20G) autoradiographic method was used to map local cerebral glucose utilization (LCGU) in the rat brain following ICV injection of BN (vehicle, BN O.1Jlg, O.5Jlg). At each dose, experiments were conducted in freely moving or restrained conditions to determine whether alterations in cerebral function were the result of BN central administration, or were the result of BN-induced motor stereotypy. The anteroventral thalamic nucleus (AV) (p=O.029), especially its ventrolateral portion (AVVL) (pincreased rates of metabolism under both restraint conditions. The effect was treatment dependent without interaction of the restraint conditions. Of all the regions that were reported to have high densities of BN receptors, the internal granular layer of the olfactory bulb (IGr) (p=O.028), and the suprachiasmatic nucleus (SCh) (p=O.003) exhibited BN treatment effects. BN effects on LCGU were also observed in the median eminence (ME) (p=O.011). Restraint, however, decreased LCGU in the lateral dorsal thalamic nucleus, ventrolateral and dorsomedial parts (LOVL and LOOM) (p=O.044, p=O.009), and the lateral geniculate (LG) (p=O.027). In sum, BN induced a marked and highly localized alteration in cerebral metabolism within parts of the anterior thalamus, which is the principle relay in the limbic circuitry. BN effects were also observed in IGr, Mi, SCh, and ME. Effects of restraint were found in LOVL, LOOM, and LG. It is suggested that increased LCGU in AV and AVVL may be the result of functional change in the limbic circuitry and the hypothalamus caused by BN receptor functional modification. In IGr, increased LCGU following BN administration is considered to be mainly the result the activation of NMB receptor, a subtype of BN receptors. In SCh, increased LCGU is believed to be caused both by BN effects on the thalamic, the hypothalamic, and the limbic functions and by activation of GRP receptor, another BN receptors subtype found in SCh. In ME, increased LCGU is suggested to be caused by BN effects on the hypothalamic functions, especially those related to the neuroendocrine functions. None of the alterations seen in these regions reflects the emission of stereotyped motor behaviors. Rather, they reflect a direct influence of BN central administration upon functioning of the cerebral regions influenced by BN administration. The restraint effects seen in LO, including LOOM and LOVL, are suggested to be the result of altered behavioral expression. The restraint effects seen in LG is suggested to be the result of reduced locomotion.

Identifying the psychosexual implications of radical radiation treatment in prostate cancer

The purpose of this study was to determine whether there was any evidence of psychosexual morbidity among men who experienced radical radiation treatment for prostate cancer. With relatively little known or available retrospective data on the psychosexual implications of radical radiation treatment in men with prostate cancer, this study posited eight research questions which provided the basis for the research. Fifty men from Southern Ontario, between the ages of 52 to 78 years, were included in the study. They had been previously randomized to a clinical trial comparing radical radiation therapy by external beam radiation, or radical radiation using a combination of a temporary iridium implant plus external beam radiation, for localized or locally advanced prostate cancer. Assessment of sexual functioning, drive, attitudes, body image, and sexual satisfaction was drawn from a multidimensional approach, since psychosexuality was viewed as having an impact on biological, psychological, and sociological domains of functioning. Medical chart reviews, semi-structured interviews, demographical profiles of each participant, and the Derogatis Sexual Functioning Inventory (DSFI) were the methods used to collect data over a four-month period. Both quantitative and qualitative research methods were incorporated in the design and evaluation of the study. Frequencies, contingency analysis, Pearson's coefficient of correlation, t-tests, and ANOVA comprised the quantitative analysis. Data obtained from audio-taped interviews were analyzed qualitatively, and used for offering further insight and for facilitating the quantitative aspect of the analysis. Overall, there was sufficient evidence to suggest psychosexual morbidity among men who were treated with radiation therapy for prostate cancer. As well,there were a number of significant findings available to answer all of the posited research questions. The most significant findings were noted in post-treatment erectile ability and sexual activity. A post-treatment change in erectile ability was reported by eighty percent of men. Sixty percent of men noted a decrease in their ability to achieve an erection by reporting some morning stiffness only, penile rigidity insufficient for penetration, decreased control of erection, and loss of spontaneous erection. Other contributing factors associated with change in erectile status were: pain or altering sensation of orgasm, blood in ejaculate, pain and decreased amount of ejaculate, and penile numbness or pain. Eighty-two percent of men experienced a post-treatment change in sexual function, primarily due to the impact of decreasing erectile status. Only seven men reported that they experienced a decrease in desire mentally, whereas the vast majority did not experience any change in desire. Changes in foreplay, stress with optimal sexual positioning, and reduced spontaneity of sex, were other factors reported with the changes in sexual activity. The findings in this study broaden our understanding of what middle- to later-aged men feel and experience as they venture onward following treatment. This was the first study that evaluated available prospective data on pre-treatment erectile status and sexual activity. As well, this study was the first (with participant compliance rates of 100 percent) to have included an interview format to capture the views of such a large number of men. This study concluded with recommendations and implications for future research and practice as we move in the direction of understanding what is necessary for preserving psychosexual well being and enhancing quality of life in men treated with radiation therapy for prostate cancer.

On the path integral formulation and the evaluation of quantum statistical averages

Four problems of physical interest have been solved in this thesis using the path integral formalism. Using the trigonometric expansion method of Burton and de Borde (1955), we found the kernel for two interacting one dimensional oscillators• The result is the same as one would obtain using a normal coordinate transformation, We next introduced the method of Papadopolous (1969), which is a systematic perturbation type method specifically geared to finding the partition function Z, or equivalently, the Helmholtz free energy F, of a system of interacting oscillators. We applied this method to the next three problems considered• First, by summing the perturbation expansion, we found F for a system of N interacting Einstein oscillators^ The result obtained is the same as the usual result obtained by Shukla and Muller (1972) • Next, we found F to 0(Xi)f where A is the usual Tan Hove ordering parameter* The results obtained are the same as those of Shukla and Oowley (1971), who have used a diagrammatic procedure, and did the necessary sums in Fourier space* We performed the work in temperature space• Finally, slightly modifying the method of Papadopolous, we found the finite temperature expressions for the Debyecaller factor in Bravais lattices, to 0(AZ) and u(/K/ j,where K is the scattering vector* The high temperature limit of the expressions obtained here, are in complete agreement with the classical results of Maradudin and Flinn (1963) .

Violent Video Game Playing, Moral Reasoning, and Attitudes Towards Violence in Adolescents: Is There a Connection?

In this study of 109 adolescents from the eighth grade of seven public elementary schools in Ontario, the relationship among adolescents’ violent video game playing patterns, habits and attitudes, their levels of moral reasoning, and their attitudes towards violence in real life was investigated. In addition, gender differences were addressed. The mixed-methodology was employed combining qualitative and quantitative data. The research results confirmed that playing video games in general is a very popular activity among those adolescents. Significant negative relationship was found between adolescents’ amount of time playing violent video games during the day and their scores on The Sociomoral Reflection Measure. Significant difference was also found between adolescents who play violent video games and those who do not play violent video games on their scores on The Attitudes Towards Violence Scale. Boys and girls significantly differed in the amount of playing video games during the day, the reasons for playing video games, their favourite video game choices, and their favourite video game character choices. Boys and girls also significantly differed on their choices of personality traits of selected video game characters, the identification with video game characters, and their mood experiences while playing video games. The findings are put into the educational context and the context of normal development, and suggestions are given for parents, for educators, and for future violent video game research.

Purification of mitochondrial RNase P in A. nidulans

Résumé La ribonucléase P (RNase P) est une ribonucléoprotéine omniprésente dans tous les règnes du vivant, elle est responsable de la maturation en 5’ des précurseurs des ARNs de transfert (ARNts) et quelques autres petits ARNs. L’enzyme est composée d'une sous unité catalytique d'ARN (ARN-P) et d'une ou de plusieurs protéines selon les espèces. Chez les eucaryotes, l’activité de la RNase P cytoplasmique est distincte de celles des organelles (mitochondrie et chloroplaste). Chez la plupart des espèces, les ARN-P sont constituées de plusieurs éléments structuraux secondaires critiques conservés au cours de l’évolution. En revanche, au niveau de la structure, une réduction forte été observé dans la plupart des mtARN-Ps. Le nombre de protéines composant la RNase P est extrêmement variable : une chez les bactéries, environ quatre chez les archéobactéries, et dix chez la forme cytoplasmique des eucaryotes. Cet aspect est peu connu pour les formes mitochondriales. Dans la plupart des cas, l’identification de la mtRNase P est le résultat de longues procédures de purification comprenant plusieurs étapes dans le but de réduire au minimum le nombre de protéines requises pour l’activité (exemple de la levure et A. nidulans). Cela mène régulièrement à la perte de l’activité et de l’intégrité des complexes ribonucléo-protéiques natifs. Dans ce travail, par l’utilisation de la technique de BN-PAGE, nous avons développé une procédure d’enrichissement de l’activité RNase P mitochondriale native, donnant un rendement raisonnable. Les fractions enrichies capables de cette activité enzymatique ont été analysées par LC/MS/MS et les résultats montrent que l’holoenzyme de la RNase P de chacune des fractions contient un nombre de protéines beaucoup plus grand que ce qui était connue. Nous suggérons une liste de protéines (principalement hypothétiques) qui accompagnent l’activité de la RNase P. IV De plus, la question de la localisation de la mtRNase P de A. nidulans a été étudiée, selon nos résultats, la majorité de la mtRNase P est attachée á la membrane interne de la mitochondrie. Sa solubilisation se fait par l’utilisation de différents types de détergent. Ces derniers permettent l’obtention d’un spectre de complexes de la RNase P de différentes tailles.

Mécanismes cellulaires et moléculaires impliqués dans la régulation du développement des circuits d’interneurones GABAergiques dans le néocortex : rôle de la molécule d’adhésion cellulaire neurale (NCAM)

Les interneurones GABAergiques constituent une population mineure de cellules par rapport aux neurones glutamatergiques dans le néocortex. Cependant ils contrôlent fortement l'excitabilité neuronale, la dynamique des réseaux neuronaux et la plasticité synaptique. L'importance des circuits GABAergiques dans le processus fonctionnel et la plasticité des réseaux corticaux est soulignée par des résultats récents qui montrent que des modifications très précises et fiables des circuits GABAergiques sont associées à divers troubles du développement neurologique et à des défauts dans les fonctions cérébrales. De ce fait, la compréhension des mécanismes cellulaires et moléculaires impliquant le développement des circuits GABAergiques est la première étape vers une meilleure compréhension de la façon dont les anomalies de ces processus peuvent se produire. La molécule d’adhésion cellulaire neurale (NCAM) appartient à la super-famille des immunoglobulines de reconnaissance cellulaire et est impliquée dans des interactions homophiliques et hétérophiliques avec d’autres molécules. Même si plusieurs rôles de NCAM ont été démontrés dans la croissance neuronale, la fasciculation axonale, la formation et la maturation de synapses, de même que dans la plasticité cellulaire de plusieurs systèmes, le rôle de NCAM dans la formation des synapses GABAergiques reste inconnu. Ce projet visait donc à déterminer le rôle précis de NCAM dans le processus de maturation des synapses GABAergiques dans le néocortex, en modulant son expression à différentes étapes du développement. L’approche choisie a été de supprimer NCAM dans des cellules GABAergiques à paniers avant la maturation des synapses (EP12-18), pendant la maturation (EP16-24), ou durant le maintien de celles-ci (EP24-32). Les méthodes utilisées ont été le clonage moléculaire, l’imagerie confocale, la culture de coupes organotypiques et des techniques morphométriques de quantification de l’innervation GABAergique. Nos résultats montrent que l’inactivation de NCAM durant la phase de maturation des synapses périsomatiques (EP16-24) cause une réduction du nombre de synapses GABAergiques périsomatiques et du branchement de ces axones. En revanche, durant la phase de maintien (EP26-32), l’inactivation de NCAM n’a pas affecté ces paramètres des synapses GABAergiques. Or, il existe trois isoformes de NCAM (NCAM120, 140 et 180) qui pourraient jouer des rôles différents dans les divers types cellulaires ou à des stades développementaux différents. Nos données montrent que NCAM120 et 140 sont nécessaires à la maturation des synapses périsomatiques GABAergiques. Cependant, NCAM180, qui est l’isoforme la plus étudiée et caractérisée, ne semble pas être impliquée dans ce processus. De plus, l’inactivation de NCAM n’a pas affecté la densité des épines dendritiques ou leur longueur. Elle est donc spécifique aux synapses périsomatiques GABAeriques. Finalement, nos résultats suggèrent que le domaine conservé C-terminal KENESKA est essentiel à la maturation des synapses périsomatiques GABAergiques. Des expériences futures nous aiderons à mieux comprendre la mécanistique et les différentes voies de signalisation impliquées.